The goals of this application are to increase the number of investigators in New Hampshire who are competitive in securing NIH funding, and to establish a Lung Biology Center that will be nationally recognized and free standing in five years. Based on a core of existing collaborative and multidisciplinary faculty at Dartmouth and Keene State College (KSC) along with other investigators in the State, COBRE funding will provide resources to develop junior faculty and infrastructure necessary to attain Center status. Faculty growth and development will be facilitated in five ways: 1) recruitment of three tenure-track faculty: two at Dartmouth, and one at Keene State College; 2) mentored development of four junior investigators already at Dartmouth, and one already at Keene State College; 3) linkage between Dartmouth, Keene State College and investigators in the State who provide expertise not available at Dartmouth; and 5) synergistic scientific collaboration through the research projects and associated administrative and proteomic cores. Under the leadership of Dr. Stanton, the current Director of the Lung Biology Program at Dartmouth, together with substantial institutional commitments, we are confident that the existing base of investigators will expand and mature with COBRE funding to an established Center, comprised of faculty who will be more competitive in obtaining NIH funding, and thereby enhance the research grant portfolio of the State. The five research projects exhibit a multidisciplinary approach characteristic of a Center and are connected by the common themes of lung biology and disease including cystic fibrosis (CF), cancer and lung injury as well as proteomics. Project 1 will examine biofilm formation in the CF lung. Project 2 will study ?F508-CFTR trafficking. Project 3 examines the structural basis of the CFTR-PDZ protein interactions that regulate the function and trafficking of CFTR. The ultimate goals of Projects 1-3, which are complementary in approach, are to elucidate the cellular mechanisms of lung disease in CF. In Project 4 the major goal is to identify biomarkers that can be used to determine causal relationships between exposure to airborne pollutants and increased incidence of cancer, obstructive airway disease and asthma. The goal of Project 5 is to use a multilevel approach using Geographic Information Systems and case-reference methods to study the environmental epidemiology of lung cancer. Together these projects will contribute to the growth of our Program and to a better understanding of the cellular and molecular mechanisms that underlie lung disease. The long-term goal of our Program is to conduct translational studies to develop new treatments and cures for lung disease.